The enzyme poly (ADP-ribose) polymerase requires DNA and catalyzes the successive transfer of ADP-ribose units from NAD to histones and other proteins associated with eukaryotic chromatin, the net results being negatively charged, short polymers covalently attached to nuclear proteins. The exact physiological function of this nuclear protein modification is still not understood, a role for the polymer in control of eukaryotic DNA replication, gene expression, chromatin condensation, and reactions resulting from a cellular need for DNA repair, have been implicated from a variety of experiments from our group and other laboratories. Protocols will be developed which extend our past evidence that the physical location of polymerase exists in the internucleosome region of chromatin substructure. The importance of poly ADP-ribosylation of histone H-1 will be related to the putative roles of this histone in chromatin super-structure (solenoid structure). Changes in chromatin substructure, upon modification, will be investigated with particular attention given to identification of chromatin proteins modified by this enzyme. An evaluation of a possible modulating role of this reaction in avian reticulocyte chromatin will be investigated with respect to the tissue specific in vitro transcription of the globin gene. BIBLIOGRAPHIC REFERENCES: "Poly (Adenosine diphosphate-ribose) Polymerase: The distribution of a Chromatin-associated Enzyme within the Chromatin Substructure", Mullins, D.W., Giri, C., Smulson, M. Biochemistry (1977) 16, 506. "Poly (ADP-ribose)" M. Smulson, S. Shall, Nature 1976 263, 14.